Ajmalicine induces the pyroptosis of hepatoma cells to exert the antitumor effect

Abstract

AbstractAjmalicine (AJM) is an alkaloid extracted from the root of Yunan Rauvolfia verticillata. At present, little research has reported the antitumor pharmacological action and mechanism of AJM. Therefore, this work aimed to conduct relevant research. The mouse hepatoma cell line H22 was intervened with a gradient concentration of AJM. Subsequently, the pyroptosis level was detected by flow cytometry. The expression of inflammatory factors and lactate dehydrogenase was measured by enzyme‐linked immunosorbent assay. Reactive oxygen species (ROS) expression was detected by dichlorodihydrofluorescein diacetate probe. In addition, the tumor‐bearing model mice were also treated with AJM to analyze tumor growth as well as the expression levels of tissue inflammatory factors and proteins. According to our results, AJM promoted the pyroptosis of H22 cells, increased the pyroptosis rate, and upregulated the expression of inflammatory factors tumor necrosis factor α, interleukin‐1β, and interleukin‐6. At the same time, it enhanced the openness of membrane pores and increased the expression of ROS. Moreover, AJM promoted the expression of Caspase‐3 and N‐terminal gasdermin E (GSDME). The AJM‐induced pyroptosis was suppressed after N‐acetylcysteine treatment to inhibit ROS, while Caspase‐3 knockdown also inhibited the AJM‐induced pyroptosis. In animals, AJM suppressed tumor growth. AJM can activate ROS to induce pyroptosis and exert the antitumor effect via the noncanonical Caspase‐3‐GSDME pyroptosis pathway.